Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of JSKN033 in Patients With Advanced or Metastatic Solid Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- RP2D( recommend Phase II dose)
研究概览
简要总结
This study is an open-label, multicenter, first-in-human, Phase I/II (dose escalation and dose expansion) study to evaluate the safety, tolerability, PK, immunogenicity and efficacy of JSKN033 in patients with advanced unresectable or metastatic solid malignant tumors that are expected to be HER2 expression (IHC ≥ 1+).
详细描述
This study is an open label, multicenter, first in human, Phase I/II (dose escalation and dose expansion) study to evaluate the safety, tolerability, PK, immunogenicity and efficacy of JSKN033 in patients with advanced unresectable or metastatic solid malignant tumors that are expected to be HER2 expression.
JSKN033 is a combination drug product comprised of JSKN003 and envafolimab for subcutaneous injection.
Phase I will be a dose escalation phase - Participants will be enrolled to receive 1.1 mg/kg , 2.3 mg/kg, 4.5 mg/kg, 5.6 mg/kg or 6.7 mg/kg, once a week.
Phase II will be a dose expansion phase - After/during dose escalation, SMC will select 1-2 dose levels to expand with additional patients with gastrointestinal tumor with HER2 expression each dose level for further exploration of the efficacy and safety of JSKN033. Once treatment is discontinued, participants will be followed up every 12 weeks for any AEs and alternative anti-cancer treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be willing and able to provide written informed consent form (ICF) for the trial.
- •Male or female, 18 years of age or older; willing and able to complete all required procedures of study.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and life expectancy ≥ 12 weeks.
- •Must have a pathologically documented advanced unresectable or metastatic solid malignant tumor (gastrointestinal tumor for dose expansion phase) with HER2 expression (IHC ≥1+) that is refractory to or intolerable with standard treatment, or for which no effective standard treatment is available. HER2 mutation in patients with NSCLC is also regarded as HER2 expression.
- •Baseline measurable disease according to RECIST 1.
- •Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Adequate organ function assessed within 7 days prior to first trial treatment [had not received blood transfusion, erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF) or other relevant medical support within 14 days before the administration of the investigational product].
- •Have adequate treatment washout period before first dose.
- •Have LVEF ≥50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to first dose.
- •Female or male patients of childbearing potential should be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 180 days after completion of study treatment. Female of childbearing potential should have a negative pregnancy test within 7 days prior to first trial treatment (childbearing potential is defined as premenopausal females without documented tubal ligation or hysterectomy, or postmenopausal females within 1 year).
排除标准
- •Patients with untreated active brain metastases or meningeal or spinal cord metastases are excluded. If the subject has received treatment for brain metastases and the metastases are stable (as evidenced by brain imaging within 28 days prior to study treatment showing stable disease, no new lesions, and no new neurological symptoms, and no requirement for steroids for at least 14 days prior to study treatment), they may be eligible for enrollment.
- •Concurrent malignancy within 5 years prior to first dose other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer, thyroid cancer not requiring treatment, ductal carcinoma in situ of the breast, or < T1 urothelial carcinoma.
- •Prior treatment with an antibody-drug conjugate (ADC) which consists of a topoisomerase I inhibitor derivative.
- •History of uncontrolled concurrent illness.
- •Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by image at screening.
- •Previous severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection either suspected or confirmed within 4 weeks prior to screening. Acute symptoms will be excluded, or must have resolved and based on investigator assessment, there are no sequela that would place participant at a higher risk of receiving investigational treatment.
- •Patients with ascites, pleural effusion, pericardial effusion which cannot be controlled by appropriate interventions.
- •Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia, grade 2 hypoparathyroidism) related to prior anticancer therapy and stable anemia not yet resolved to grade ≤ 1 (NCI-CTCAEV5.0).
- •Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief course of corticosteroids for the prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- •History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or excipients in JSKN033 drug formulation.
- •Prior history of anti-HER2 therapy induced angioedema, or severe hypotension and Severe allergic reactions to other antibody drugs or topoisomerase I inhibitors.
- •Other conditions that, in the investigators' opinion, would make patients inappropriate to participate in this study, such as a history of mental illness, alcoholism or drug abuse.
研究组 & 干预措施
Dose escalation/expansion
The dose escalation phase will utilize single patient accelerated dose titration (ADT) for dose level 1 (1.1 mg/kg , SC, QW) and dose level 2 (2.3 mg/kg, SC, QW), followed by dose level 3 (4.5 mg/kg, SC, QW), dose level 4 (5.6 mg/kg, SC, QW) and dose level 5 (6.7 mg/kg, SC,QW), which will all be enrolled and monitored using the "3+3" design, aimed at determining the MTD/RP2D of JSKN033.
After or during dose escalation, SMC will select 1-2 dose levels to expand with 10-30 additional patients with gastrointestinal tumor with HER2 expression each dose level for further exploration of the efficacy and safety of JSKN033.
干预措施: JSKN033 Injection (Drug)
结局指标
主要结局
RP2D( recommend Phase II dose)
时间窗: Postdose of last participant up to 1 year
To determine RP2D of JSKN033
DLTs （Dose-limiting toxicities）
时间窗: Baseline up to 21 days after the first dose
DLTs are defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.
Incidence and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), assessed by CTCAE V5.0
时间窗: Postdose of last participant up to 1 year
Clinically significant changes in physical examination findings, vital sign measurements, standard clinical laboratory parameters, 12-lead electrocardiogram (ECG) parameters, ECHO cardiography or multiple-gated acquisition (MUGA) scan findings will be recorded as AEs.
Objective Response Rate (ORR) Following Treatment With JSKN033 in Participants With Advanced Solid Malignant Tumors
时间窗: From 6 weeks postdose of last participant up to 1 years
Objective response rate (ORR) by investigators' review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Overall Survival (OS) Following Treatment With JSKN033 in Participants(Postdose of last participant up to 1 year)
- Progression-Free Survival (PFS) Following Treatment With JSKN033 in Participants(Postdose of last participant up to 1 year)
- Duration of Response (DoR) Following Treatment With JSKN033 in Participants(Postdose of last participant up to 1 year)
- Maximum concentration (Cmax)(Postdose of last participant up to 1 year)
- Time at which Cmax is reached (Tmax)(Postdose of last participant up to 1 year)
- Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast)(Postdose of last participant up to 1 year)